Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Erdafitinib · 9 trials · 6 indications
Overall survival was measured from the date of randomization to the date of the participant's death.
RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or carcinoma in situ \[CIS\]), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and computed tomography (CT)/ magnetic resonance imaging (MRI) urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment. The Kaplan-Meier method was used to estimate the distribution of overall RFS for each treatment group.
ORR is defined as the percentage of participants who achieved a complete response (CR), or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information.
ORR is defined as the percentage of participants who achieved a CR, or PR based on RANO criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information. The core panel cohort is a subgroup of the broad panel cohort with a select panel of pre-specified FGFR markers: FGFR3 mutations (S249C;Y373C; R248C; G370C); FGFR2 mutations (C382R); FGFR3 fusions (FGFR3-TACC3); FGFR2 fusions (FGFR2-BICC1; FGFR2-TACC2).
Objective Response Rate (ORR) is defined as proportion of participants with best objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
Percentage of participants with best (overall) objective response were reported. Best objective response is defined as the best (overall) objective response a participants achieved during the study in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), where CR and PR were confirmed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responders are participants with BOR of CR or PR.
Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.
Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of midazolam alone or in combination with erdafitinib.
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of metformin alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of midazolam alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of 1-OH-Midazolam alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of metformin alone or in combination with erdafitinib
Cmax is defined as the maximum observed plasma of erdafitinib concentration.
AUC (0-168 hours) is defined as the area under the plasma analyte concentration-time curve from time 0 to one week postdose (168 hours).
AUC (0-last) is defined as area under the plasma analyte concentration-time curve from time 0 to time of the last observed quantifiable concentration.
AUC (0-infinity) is defined as the area under the analyte concentration-time curve from time 0 to infinite time.
Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.
ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.
The Cmax is the maximum observed plasma analyte concentration.
Area under the plasma analyte concentration-time curve from time 0 to one week post-dose (168 hours).
\[(AUC)0-last\] is defined as area under the plasma analyte concentration-time curve from time 0 to time of the last observed quantifiable concentration (Clast).
\[(AUC)0-infinity\] is defined as the area under the analyte concentration-time curve from time 0 to infinite time, calculated as the sum of AUClast and Clast/lambda (z), in which Clast is the last observed quantifiable concentration and lambda (z) is the first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
The Cmax is the maximum observed plasma concentration.
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 (Arm 1A): Erdafitinib | EXPERIMENTAL | Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision. |
| Cohort 1 (Arm 1B): Vinflunine or Docetaxel | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system. |
| Cohort 2 (Arm 2A): Erdafitinib | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision. |
| Cohort 2 (Arm 2B): Pembrolizumab | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first. |
| Cohort 1: Erdafitinib | EXPERIMENTAL | Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ \[CIS\], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib. |
| Cohort 1: Investigators Choice | ACTIVE_COMPARATOR | Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC) or hyperthermic MMC. Participants who are randomized to gemcitabine or MMC or hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib. |
| Cohort 2 | EXPERIMENTAL | Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib. |
| Cohort 3 | EXPERIMENTAL | Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib. |
| Erdafitinib | EXPERIMENTAL | Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved. |
| Erdafitinib (8 milligram) | EXPERIMENTAL | Prior to interim analysis 1 (IA1), there were 2 treatment regimens: Regimen 1 (10 milligram \[mg\] once daily, 7 days on/7 days off); and Regimen 2 (6 mg once daily for 28 days). Following IA1, Regimen 1 is closed for further enrollment and starting dose of Regimen 2 is increased to 8 mg once daily for 28 days on a 28-day cycle (referred to as Regimen 3). Participants who enrolled in DDI substudy will receive pretreatment with single doses of midazolam (Day -2) and metformin (Day -1). Participants enrolled in DDI substudy will receive 8 mg erdafitinib treatment from Day 1 to Day 15, single doses of midazolam 2.5 mg (Day 13) and metformin 1000 mg (Day 14) and erdafitinib treatment will continued until disease progression. Participants who completed the DDI substudy and continue to benefit from erdafitinib treatment, will continue to receive erdafitinib in long-term extension (LTE) phase. |
| Erdafitinib and Carbamazepine | EXPERIMENTAL | Participants will receive single oral dose of erdafitinib dose 1 on Day 1 30 minutes after the start of a standardized breakfast in Period 1 followed by repeated doses of carbamazepine orally every 12 hours from Days 15 to 35 (carbamazepine Dose 1 from Days 15 to 17, Dose 2 from Days 18 to 20, and then Dose 3 from Days 21 to 35) 30 minutes after the start of standardized meal (breakfast and dinner) in Period 2. After 8 Days of Dose 3 carbamazepine treatment, on Day 28, participants will receive a single oral dose of erdafitinib dose 1 with that day's carbamazepine dose. |
| Phase 1b: Dose Escalation | EXPERIMENTAL | Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. |
| Phase 2: Dose Expansion | EXPERIMENTAL | The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV). |
| Treatment A: Erdafitinib alone | EXPERIMENTAL | Participants will receive single 4 milligram (mg) oral dose of erdafitinib on Day 1 in a fasted state. |
| Treatment B: Erdafitinib + Fluconazole | EXPERIMENTAL | Participants will receive 400 mg fluconazole once daily orally from Day 1 to Day 11 in a fasted state and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 400 mg fluconazole dose. |
| Treatment C: Erdafitinib + Itraconazole | EXPERIMENTAL | Participants will receive 200 mg itraconazole once daily orally from Day 1 to Day 11 and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 200 mg itraconazole dose. |
| Treatment Sequence 1: Erdafitinib 9 mg | EXPERIMENTAL | Participants will receive 9 milligram (mg) dose of erdafitinib under fasted condition \[Treatment A\] in Period 1, and under fed (with high-fat and high-calorie breakfast) condition \[Treatment B\] in Period 2. Each Treatment Period will be separated by a washout of at least 28 days. |
| Treatment Sequence 2: Erdafitinib 9 mg | EXPERIMENTAL | Participants will receive 9 mg dose of erdafitinib under fed (high-fat and high-calorie breakfast) condition \[Treatment B\] in Period 1, and under fasted condition \[Treatment A\] in Period 2. Each Treatment Period will be separated by a washout of at least 28 days. |
| Name | Type | Description |
|---|---|---|
| Erdafitinib | DRUG | Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg. |
| Vinflunine | DRUG | Participants will receive vinflunine 320 mg/m\^2 as a 20-minute intravenous infusion. |
| Docetaxel | DRUG | Participants will receive docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion. |
| Pembrolizumab | DRUG | Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion. |
| Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA) | DEVICE | FGFRi CTA will be used to determine molecular eligibility. |
| Investigator Choice (Gemcitabine) | DRUG | Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months. |
| Investigator Choice (Mitomycin C) | DRUG | Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months. |
| Midazolam | DRUG | Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13. |
| Metformin | DRUG | Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14. |
| Carbamazepine | DRUG | Participants will receive an oral dose of carbamazepine tablets from Day 15 to 35 in Period 2. |
| Cetrelimab | DRUG | Participants will receive cetrelimab by intravenous infusion. |
| Cisplatin | DRUG | Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy. |
| Carboplatin | DRUG | Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy. |
| Fluconazole | DRUG | A 400-mg fluconazole orally (4\*100 mg capsules) will be administered from Day 1 to Day 11. |
| Itraconazole | DRUG | A 200-mg itraconazole orally (2\*100 mg capsules) will be administered from Day 1 to Day 11. |
Inclusion Criteria: * Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than \[\<\] 50 percent \[%\] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or microp...
Erdafitinib is an investigational small molecule being studied for the treatment of urinary bladder neoplasms, urothelial cancer, urothelial carcinoma, and advanced solid tumors. It is also being evaluated in healthy participants for pharmacokinetic studies. The drug is currently in Phase 2 clinical development for oncology indications.
Erdafitinib targets fibroblast growth factor receptors (FGFR), specifically FGFR1, FGFR2, FGFR3, and FGFR4. It is a tyrosine kinase inhibitor that blocks these receptors, which are involved in cancer cell growth and survival. This mechanism is being investigated in the treatment of urothelial cancer and other solid tumors.
Erdafitinib is developed by Johnson & Johnson, a company traded on the New York Stock Exchange under the ticker JNJ. The drug is being studied in clinical trials for oncology indications, including urothelial cancer and advanced solid tumors.
Erdafitinib is in Phase 2 clinical development for oncology indications. It is an investigational drug and has not been approved by the FDA. The drug is being studied in clinical trials for urinary bladder neoplasms, urothelial cancer, and advanced solid tumors.
Erdafitinib has been studied in several clinical trials. NCT02699606 is a Phase 2 study in Asian participants with advanced non-small-cell lung cancer, urothelial cancer, esophageal cancer, or cholangiocarcinoma. Other trials include NCT03066687, NCT03135106, and NCT04330248, which are Phase 1 studies in healthy participants.
Yes, Erdafitinib is also known as JNJ-42756493. The drug is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being developed by Johnson & Johnson for the treatment of urothelial cancer and other solid tumors.